CRISPR Therapy to Enter Trials

Researchers in China will use the CRISPR-Cas9 system to edit T cells extracted from patients with cancer before those cells are returned to the body to target malignant ones.

Jul 25, 2016

Jef Akst

WIKIMEDIA, ED UTHMANOncologist You Lu of Sichuan University’s West China Hospital in Chengdu and colleagues will soon begin trialing a new CRISPR-based immunotherapy in 10 patients with non-small cell lung cancer that has metastasized and is not responding to treatment. The hospital’s review board approved the study on July 6, and the team hopes to treat the first patient next month, according to Nature.

Meanwhile, a similar project proposed by researchers at the University of Pennsylvania and elsewhere was greenlighted by a US National Institutes of Health (NIH) advisory panel, but “faces months of additional regulatory hurdles before it can go ahead by the end of 2016 at the earliest,” STAT News reported.

Lu’s team may have beaten the US group for regulatory approval, but it wasn’t easy, Lu told Nature. “There was a lot of back and forth,” he said, noting that it took six months and a lot of time and resources. He also added that the NIH’s approval of the proposed trial by UPenn researchers “strengthened ours and our IRB’s confidence in this study.”

Once the trial gets underway, Lu and colleagues will remove T cells from patients’ blood, then use the CRISPR-Cas9 system to delete the PD-1 gene, eliminating the surface receptor that binds tumor-produced ligands and tells the immune cells not to fight the cancer. The edited T cells would then be expanded in culture and those that are missing only their PD-1 gene will be infused back into patients. The trial is slated to include a total of 10 patients, but the researchers plan to start with just one, and slowly increase to three different dosage regimens in the remaining patients.

“It’s an exciting step forward,” UPenn’s Carl June, an immunotherapy pioneer and a scientific adviser on the proposed US trial, told Nature. (The US trial would similarly knock out the PD-1 gene, but would also make two other genetic alterations in the cells before they are infused into the patients.)